Tricky… [RSABE / ABEL]

posted by Mikalai  – Belarus, 2020-01-30 12:08 (357 d 18:58 ago) – Posting: # 21102
Views: 13,845

(edited by Mikalai on 2020-01-30 14:08)

Dear Helmut,

» Tricky. In your original post you stated also a decision tree. Any of these decisions made can be wrong, which will inflate the TIE. Imagine you failed ABE not because the reference is highly variable but by lacking power. Then you would continue to #2. The observed CVwR was >30% by chance and you expand the limits. However, the true CVwR (in the patient population) is ≤30%, and the decision wrong – inflated TIE (see there). More in the answer to #4.

It is a bit confusing, but could you clarify a couple of points.
  1. In the case of going by the ABE path (see the decision tree), I assume we do not use any population parameters and just compare concentrations from samples. There is no inflation TIE? Is it correct? And we do not use RR for the ref drug in our calculation. Is it correct?
  2. But if the study fails, we then calculate RR and a new bioequivalence interval if CV is higher than 30%. That is when we use RR and where TIE can be inflated. Is it correct? But we do not recalculate our new CI we just use that from ABE to compare with a new or the old CI. In the latter case, we basically fail the study. Is it correct?
The identical decision tree was used in the BS of rasagiline (registration required) and was accepted by EMA.
If I am correct, in my view it is a preferable solution to minimize the inflation TIE.
Best regards

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